排毒保肾丸对糖尿病肾病大鼠炎症小体NLRP3表达及NF-κB信号通路的影响  

Effect of Paidu Baoshen Pill on expression of inflammatory bodies NLRP3 and NF-κB signaling pathway in rats with diabetic kidney disease

作　　者：李敬[1] 乔丽丽 张丽敏[1] 高燕[1] 樊星[1] 田领 LI Jing;QIAO Lili;ZHANG Limin;GAO Yan;FAN Xing;TIAN Ling(Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院,保定071000

出　　处：《中国免疫学杂志》2023年第7期1437-1441,共5页Chinese Journal of Immunology

基　　金：保定市科技计划项目(2041ZF298)资助。

摘　　要：目的:探究排毒保肾丸对糖尿病肾病(DKD)大鼠炎症小体核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)表达及核转录因子-κB(NF-κB)信号通路的影响。方法:48只大鼠随机分为4组:对照组、模型组、排毒保肾丸组、阳性对照组(氯沙坦组)。模型组、排毒保肾丸组和氯沙坦组建立DKD大鼠模型,饲以高脂高糖饲料并腹腔注射小剂量链脲佐菌素(STZ)。排毒保肾丸组、氯沙坦组分别灌胃排毒保肾丸、氯沙坦,对照组、模型组灌胃给予等量生理盐水,连续8周。8周后测定尿蛋白、血肌酸酐、血尿素氮含量,处死大鼠并留取肾脏组织。ELISA检测血清IL-6、IL-1β及TNF-α含量;HE染色观察肾脏组织形态学改变;Masson染色观察肾脏组织纤维化改变;免疫组化染色及Western blot检测NLRP3、NF-κB p65、天冬氨酸特异性蛋白酶1(Caspase-1)蛋白表达。结果:与对照组相比,模型组大鼠肾脏组织损伤严重,尿蛋白、血肌酐、尿素氮含量、炎症因子IL-1β、IL-6、TNF-α含量、NLRP3、NF-κB p65、Caspase-1蛋白表达显著增加(均P<0.05);与模型组相比,排毒保肾丸组和氯沙坦组肾脏组织损伤减轻,尿蛋白、血肌酐、尿素氮含量、炎症因子IL-1β、IL-6、TNF-α含量、NLRP3、NF-κB p65、Caspase-1蛋白表达显著减少(均P<0.05)。结论:排毒保肾丸能够有效改善DKD损伤,抑制机体炎症反应,可能通过抑制炎症小体NLRP3表达和NF-κB信号通路发挥保护作用。Objective:To explore effect of Paidu Baoshen Pill on expression of inflammatory body nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and nuclear transcription factor-κB(NF-κB)signal in rats with diabetic kidney dis-ease(DKD).Methods:Forty-eight rats were divided into 4 groups randomly:Control group,Model group,Paidu Baoshen Pill group,and positive control group(Losartan group).DKD rat models were established in Model group,Paidu Baoshen Pill group and Losartan group,fed with high-fat and high-sugar diet and intraperitoneal injection of small dose of streptozotocin(STZ).Paidu Baoshen Pill group and Losartan group were given Paidu Baoshen Pill and losartan by gavage respectively,Control group and Model group were given same amount of normal saline by gavage for 8 weeks.After 8 weeks,urine protein,blood creatinine and blood urea nitrogen were measured.Rats were killed and kidney samples were collected.ELISA was used to detect serum IL-6,IL-1βand TNF-αlevels;HE staining was used to observe morphological changes of kidney tissue;Masson staining was used to observe kidney tissue fibers chemi-cal changes;immunohistochemical staining and Western blot were used to detect expressions of NLRP3,NF-κB p65,aspartate-specific protease-1(Caspase-1)protein.Results:Compared with Control group,kidney tissue of Model group was severely damaged,contents of urine protein,blood creatinine and urea nitrogen,contents of inflammatory factors IL-1β,IL-6,TNF-α,NLRP3,NF-κB p65,Cas-pase-1 protein expressions were increased significantly(all P<0.05);compared with Model group,Paidu Baoshen Pill group and Losartan group had less kidney tissue damage,contents of urine protein,blood creatinine,urea nitrogen,contents of inflammatory factors IL-1β,IL-6,TNF-α,NLRP3,NF-κB p65,and Caspase-1 protein expressions were significantly reduced(all P<0.05).Conclusion:Paidu Baoshen Pill can effectively improve DKD injury and inhibit body's inflammatory response,which may play a pro-tective effect by inhibiting expressions of i

关 键 词：排毒保肾丸 糖尿病肾病 核苷酸结合寡聚化结构域样受体蛋白3 核转录因子-ΚB 

分 类 号：R587.2[医药卫生—内分泌]